META-ANALYSIS OF HVEM EXPRESSION IN BREAST AND BRAIN CANCE

ASAD, ANTONELA S; GONZALEZ, NAZARENO; PEÑA AGUDELO, JORGE A.; NICOLA CANDIA, ALEJANDRO J; GARCIA FALLIT, MATÍAS; SEILICOVICH, ADRIANA; CANDOLFI, M

Congreso; Reunión anual de la SAIC; 2021

HVEM is an immunological checkpoint with dual immunomodulatory function; while its binding to LTα and LIGHT favors T cell activation, its binding to CD160 and BTLA suppresses their function. Thus, HVEM has emerged as an interesting therapeutic target for enhancing antitumor immune responses. Since HVEM expression has been detected in breast cancer (BRCA) and glioma biopsies, we performed a meta-analysis of transcriptomic data from The Cancer Genome Atlas to assess the expression of HVEM in these tumors. In BRCA biopsies, we found that HVEM expression is higher in normal vs. tumoral tissue, being lower in triple negative BRCA (TNBC) biopsies than in other BRCA subtypes. In TNBC, the expression of HVEM correlated with the expression of lymphocytic activation markers such as HLA-DR (r: 0,7109) and CD69 (r: 0,6013), but also with exhaustion markers as CTLA4 (r: 0,6349), PDL1 (r: 0,5331), LAG3 (r: 0,6547) and TIM3 (r: 0,6663). Even though HVEM expression did not show association with TNBC patient survival, its expression was positively correlated with the expression of gene signatures corresponding to helper and cytotoxic T cells, Tregs, macrophages and dendritic cells (DC). As for glioma biopsies, HVEM expression was higher in gliomas carrying wild-type IDH, an enzyme whose mutation has been recently associated with better prognosis. In addition, HVEM expression correlated with the aggressiveness of glioma subtypes, being higher in glioblastoma (GBM). In GBM, HVEM positively correlated with HLA-DR (r: 0,5021), CD69 (r: 0,4460), CTLA4 (r: 0,3721), PDL1 (r: 0,3725) and TIM3 (r: 0,5136). Although HVEM expression was not associated with patient survival, it correlated with the expression of helper and cytotoxic T cells, DC and macrophages. These results suggest that the pathways triggered by HVEM may have different outcomes depending on the tissue and tumor subtype, and that this checkpoint should be studied in depth as a target for cancer treatment.